Production of IFN-gamma and IL-10 to Shigella invasins by mononuclear cells from volunteers orally inoculated with a Shiga toxin-deleted Shigella dysenteriae type 1 strain

Volunteers were orally administered invasive, non-Shiga toxin-producing Shi gella dysenteriae 1 to establish a challenge model to assess vaccine effica cy. In stepwise fashion, four separate groups were given 3 x 10(2), 7 x 10( 3), 5 x 10(4), or 7 x 10(5) CFU, Using PBMC, proliferative responses and cy tokine production were measured to S, dysenteriae whole-cell preparations a nd to purified recombinant invasion plasmid Ags (Ipa) C and IpaD, Anti-LPS and anti-Ipa Abs and Ab-secreting cells were also evaluated. Preinoculation PBMC produced considerable quantities of IL-10 and IFN-gamma, probably sec reted by monocytes and NK cells, respectively, of the innate immune system. Following inoculation, PBMC from 95 and 87% of volunteers exhibited an inc reased production of IFN-gamma and IL-10, respectively, in response to Shig ella Ags, These increases included responses to IpaC and IpaD among those v olunteers receiving the lowest inoculum, No IL-4 or IL-5 responses were det ected. Whereas there were no Ab or Ah-secreting cell responses in volunteer s receiving the lowest inoculum, other dose groups had moderate to strong a nti-LPS and anti-Ipa responses. These results suggest that in humans, type I responses play an important role in mucosal and systemic immunity to S, d ysentariae 1.